Fungal better Flashcards
how has evoltion affected fungal infections
they are often chronic and recurrent
unicellualr
yeast
filamentous
mutlicellular
endemic mycoses
only prevalent i regions with distinct climate conditions
spore
air-borne- can reach terminal air-spaces e.g. Aspergillus fumigatus
innate- the host recongises
conserved cell wall constituents
what are the conserved cell wall constituents
B-glucans (1-3;1-6), chitin and galactans
name two innate PRRs which recognise Fungal FAs
Dectin -1 and TLRs
where are Dectin-1 receptors highly conserved
on the surface of dendritic cells and lesser amounts on macrophages
which part of the dectin-1 receptor recognises B-glucans
the C-type lectin carbohydrate recognition domain
zymosan
cell wall fragments consisting of B-glucans, mannans, mannoproteins and chitin
what happens when a fungal FA engages with a Dectin -1
1) B-glucan binds to dectin-1 via c-type lectin carbohydrate recognition domain
2) engagement of dectin-1 results in tyrosine phosphorylation of its cytoplasmic immunoreceptor (ITAM)
3) acts synergistic ally with TLRs to induce production of cytokines and produce ROS
together TLRs and Dectin-1 cause
innate inflammation
TLRs play a pivotal role in
distinguishing between apoptotic particles produced by normal tissue turnover and particles indicative of infection
why are TLRs and TLRs not only important for innate inflammation
also cause maturation of dendritic cells- initiating adaptive immune response
stimulation of TLRs leads to
production of pro-inflammatopry cytokines
most TLRs signal through
MyD88
MyD88
adaptor protein which binds to TLR following activation
Candida albicans is a
commensal fungus, found in normal human flora
where is candida albicans found
oral, gastrointestinal and urogenital tracts
what leads to persistent mucosal infection in CA
disruption of mucosal barriers
thrush
- superficial mucosal infection
candia esophagitis
common infection within HIV patients.
in immunocompromised patients CA infections
can disseminate to cause life-threatening infections in any organ
collaborative signalling
involves both TLR and dectin-1 signalling at the same time to cause enhanced cytokine production
what is TLRs adaptor protein
MyD88
what id dectin-1 adaptor protein
Syk
fungi and complement: candida express surface adhesion and mannoproteins whichactivate
alternative and lectin pathways
Mannose Binding lefctin is a
collectin- opsonin
MASPS
mannose-binding lectin associated serine proteases
what do MASPs do
couple collectins to the complement pathway
MASPs before ligand binding
lack protease ability
after ligand bidding MASPs
bidning of MBL leads to a conformation change, promoting proteolytic activity of MASPs- intitating complement cascades
defence against Candida infection
-activation of complement results in phagocytosis by neutrophilsa nd macrophages
phagocytosis triggers
production of ROS
interaction of cell wall componeents (mannoprotein, B-glucans and chitins) with phagocyte receptors such as TLR and dectin-1 stimualtes the release of
IL-1, IL-6, TNF (released by neutrophils)
IL-1, IL-6 and TNF
promotes mature of dendritic cells- increasing adaptive response
Chromoblastomycosis and Fonsecaea pedrosoi
- non fatal
- subcutaneous
- occurs after transcutaneous trauma
- chronic
- hard to treat (anti-fungals and surgery)
treatment for Chromoblastomycosis and Fonsecaea pedrosoi involves
trying to stimulate both TLR and Mincle to promtoe enhanced cytokine release
- Chromoblastomycosis and Fonsecaea pedrosoi only stimulates Mincle response and not TLR
wwhat is given to treat Chromoblastomycosis and Fonsecaea pedrosoi and why??
Pam3 CSK4
- makes sure TLR2 is also stimulated
name three different receptors that recognise fungi and their adaptive proteins
TLR- Myd88
Dectin- Syk
Mincle- Syk
Pam3CSK4
A TLR 2 agonist!
Given to patients with chromblastomycosis- to help stimulate both TLR2 response and Mincle –> enhanced cytokine signalling –> enhanced immune response
